Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions.

We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis.

Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC.

AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2024 Oct 04 [Epub ahead of print]

Lucia Osorio, Tatiana P Grazioso, Guillermo de Velasco, Olatz Etxaniz, Jose Luis Pérez-Gracia, Álvaro Pinto, Ignacio Durán, Enrique Grande, Pablo Borrega Garcia, Martín Lázaro, Laura Rodriguez, Maria Laura Villalobos, Lourdes García, Andrés Cuellar, María Pilar Solís-Hernández, Cristina Pernaut, Juan Francisco Rodríguez-Moreno, Cristina Rodriguez-Antona, Jesús García-Donas

Servicio de Urología, Urología Hospitalaria, Hospital HM La Rosaleda, Santiago de Compostela, Spain., Instituto de Investigación Sanitaria HM Hospitales (IISHM), Madrid, Spain., Hospital Universitario 12 de Octubre, Madrid, Spain., Grupo de Investigación Aplicada en Oncología de Badalona (B·ARGO), Hospital Germá Trials I Pujol, Barcelona, Spain., Clínica Universidad de Navarra, Pamplona, Spain., Medical Oncology Department, Hospital Universitario La Paz - IdiPAZ, Madrid, Spain., Hospital Universitario Marqués de Valdecilla, Santander, Spain., Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain., Hospital Universitario de Cáceres, Cáceres, Spain., Hospital Álvaro Cunqueiro, Vigo, Spain., Hospital Universitario de Fuenlabrada, Madrid, Spain., Hospital Universitario Príncipe de Asturias, Madrid, Spain., Hospital de Segovia, Segovia, Spain., Institut Català d'Oncologia, Badalona, Spain., Hospital Universitario Central de Asturias, Oviedo, Spain., Hospital Universitario Severo Ochoa, Madrid, Spain., Pharmacogenomics and Tumor Biomarkers Group, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC/UAM, Madrid, Spain. ., Instituto de Investigación Sanitaria HM Hospitales (IISHM), Madrid, Spain. .